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cium concentration; reducing urine oxalatesmay have a more
powerful effect on stone for-mation than can reduction of urine
calcium. Pa-tients with calcium oxalate stones, particularlythose
with documented hyperoxaluria, shouldavoid foods high in oxalates.8
Moreover, vitaminC is a precursor to endogenous production
ofoxalates, so some clinicians recommend avoid-ing mega-doses of
vitamin C. The rare geneticcondition of primary hyperoxaluria is
only
slightly impacted by dietary reduction, andcauses serious
medical problems besides kidneystones. The effect of excess animal
protein(purine) is also most obvious for the uric acidstone former.
Uric acid, a by-product of purinemetabolism, is excreted in large
quantities in theurine. Excess protein creates urine with hightotal
urine uric acid, potentially high super satu-ration of urine uric
acid, and a low pH, neces-sary for formation of uric acid stones.
There isno inhibitor of uric acid crystal formation, sodietary
measures focus on reducing uric acid
and increasing urine volume.9
In regard to this,reduction of animal protein to 12
ounces per dayfor adults is recommended. This is plenty tomeet the
dietary needs of most population inIndia, many of whom typically
consume severalmore ounces of animal protein daily than is
rec-ommended. Protein from plant sources (beans,legumes, etc.) can
be substituted as a dietaryalternative without negative
consequences how-ever calcium oxalate stone formers reducing
their animal protein should also note the oxalatecontent of
substitute proteins. The role of excessprotein in promoting calcium
stone formation isless obvious, but equally important. High
die-tary protein is associated with increased urinarycalcium. Thus,
there is a link between meat con-sumption and both uric acid and
calcium stoneformation.10 Therefore, the benefits of
proteinrestriction for stone formers are many. It has
been reported that super saturation of urinary
lithogenic promoters such as calcium, oxalate,phosphate and uric
acid mostly obtained fromthe diet are considered as the risk
factors of renalstone formation. On the other hand, a
decreasedurinary concentration of stone inhibitors such ascitrate,
potassium and magnesium is also a criti-cal risk. The urinary
levels of these stone modu-lators are greatly influenced by
diet.
CANDIDATE GENES FOR UROLITHIASIS
Genetic factors are known to play a role in
urolithiasis. Studies have tried to identify genesrelated to
ureter calculi in an effort to clarify thecause of urolithiasis and
to advance the diagno-sis and treatment of urolithiasis.11,12
It has beenreported that the use of single-nucleotide
poly-morphisms (SNPs) associated with genetic dis-eases has been
fruitful in identifying candidatedisease genes. Recent genetic
advances in uro-lithiasis indicate the potential of a new
approachtowards the gene polymorphism.9,13-15 Moreover,
Birla Singh and Sailo
Major Type Subtypes
Calcium Stone (70-80%)
Calcium oxalate monohydrate (40-60%)
Calcium oxalate dehydrate (40-60%)
Calcium hydrogen phosphate (brushite) (2-4%)
Calcium orthophosphate (
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172 Science Vision © 2013 MAS. All rights reserved
polymorphism in manganese superoxide dismu-tase gene (Mn-SOD) is
a new approach to iden-tify its probable association with
urolithiasisthrough oxidative stress. MnSOD is one of the
primary enzymes that directly scavenge poten-tial harmful
oxidizing species. It has been re-ported that A valine (Val) to
alanine (Ala) sub-stitution at amino acid 16, occurring in the
mito-chondrial targeting sequence of the MnSODgene, has been
associated with an increase inurolithiasis risk.16 Moreover,
number of studieshas been carried out by many scientists in
manyparts of the world to identify the probable candi-date genes
responsible for urolithiasis. Some ofthe results as reported from
the studies done bythe scientists are shown in Table 2.
As numerous studies have been dedicated tointerpreting the
possible association between thepolymorphisms of genes and
urolithiasis suscep-tibility. However, the results were remained
in-conclusive. The controversial results acrossmany of these
studies could possibly be relatedto the small sample size from an
individualstudy, ethnic difference or the biological geneticmodel
applied for the analysis. Therefore, it wasnecessary to quantify
the potential between-study heterogeneity and summarize results
fromall eligible studies with rigorous methods. In
view of this, very recently, Yiwei Lin et al .20
car-ried out a meta-analysis with the most updateddata in order
to revisit the association betweenVDR (vitamin-D receptor) variants
(i.e., ApaI,
BsmI, Fok I and Taq I) and urolithiasis
risk andreported that some VDR gene polymorphismsare associated
with an increase in the probabilityof urolithiasis with certain
populations under anindicated genetic model. Considering the
predic-tive value, this meta-analysis study also warrants
further investigation in this field to better clarifythese
SNP-urolithiasis associations and to rein-force their findings.
STATUS OF UROLITHIASIS IN NORTHEAST IN-
DIA
The northeastern states of India, which bor-der Burma (Myanmar)
on one side and can besaid to fall in the broad belt area of stone
diseasecovering south-east, middle-east, north-east Asiaand facing
an acute problem of stone diseases.Due to lack of research
facilities, the remote-ness, difficult geographical situations, the
preva-lence of urolithiasis is are virtually unknownoutside of
these states. A preliminary surveyfrom the laboratory highlighted
the fact that uro-lithiasis is a major problem in these regions
andrequired urgent attention.21 It is commonly be-lieved that
almost every family has a memberafflicted with this disease. The
incidence of uro-lithiasis is very high among the natives of
theseregions who are different in food habits, andalso socially,
culturally and ethnically from thepeople of the mainland of India.
Most of theliving population in these states have differentfood
habits like rice as staple diet, high con-sumption of fermented
fishes, soybeans, bam-
boos and other types of indigenous food
stuffs.Non-vegetarian foods are one of the major reci-pes in the
daily menu of the most of the peopleliving in this region. But
study of literatures re-vealed that there have been non-existent of
dataon the studies of etiologic chemical factors ofurolithiasis
found in the in the different vegeta-
bles and meat foodstuffs commonly availableand consumed by
the natives of this region.Moreover, no publish literature have
been re-
Table 2. Candidate genes and type of patients as reported by
different studies.
Candidate Genes Type of patients References
TaqI and A paI gene polymorphism Calcium stone patients
Nishijima et al.17
BsmI endonuclease polymorphism Calcium oxalate stone
patients Wen-Chi Chen et al.18
VEGF gene BstUI polymorphism Calcium oxalate stone patients
Chen et al.15
FokI and TaqI VDR genes polymorphism Calcium oxalate stone
patients Mittal et al.19
Understanding epidemiology and etiologic factors of
urolithiasis: an overview
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Science Vision © 2013 MAS. All rights reserved 173
ported on marker genes polymorphism for thisdisease from this
region of India. In fact, thefollowing key questions are still
needed to con-sider as far as the prevalence of urolithiasis inthe
northeastern states of India is concern.
1. Why the prevalence of urolithiasis is veryhigh in the living
population of north east-ern states of India as compared tomainland
India? And is the epidemiologyof urolithiasis endemic to this
region only?
2. Is the different dietary habits of the nativesof this region
playing any role for the highprevalence of urolithiasis?
3. Is genetic factor playing a role in thepathogenesis of
urolithiasis in the nativesof this region?
4. Is different climatic condition from otherparts of the
country play a major role forthe epidemiology of urolithiasis in
thisregion?
5. What are the remedies and preventivemeasures which can be
look out by thescientist and health professionals to con-tain this
disease?
CONCLUSION
In view of the conflicting data reported fromother parts of the
world on the role of diet andgenetic factors in the pathogenesis of
urolithi-asis, further in-depth studies are still needed sothat
finding from such studies may be of greatimportance both as a guide
for the clinical man-agement and also for better understanding
ofphysicochemical principles underlying the for-mation of calculi
that may help to give adviceand suggestions for the people and
patients to
carry out preventive measures in reducing therisk of prevalence
and recurrence of urolithiasisand the present article have
highlighted some ofthe aspect of this diseases.
ACKNOWLEDGEMENTS
Thanks are due to Department of Biotechnol-ogy, Ministry of
Science and Technology Gov-
ernment of India for providing financial assis-tance to K. Birla
Singh, under Twining MajorResearch Project.
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